Skip to main content

Research Repository

Advanced Search

All Outputs (58)

CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans (2024)
Journal Article
White, C. W., Platt, S., Kilpatrick, L. E., Dale, N., Abhayawardana, R. S., Dekkers, S., …Hill, S. J. (2024). CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans. Science Signaling, 17(828), Article abl3758. https://doi.org/10.1126/scisignal.abl3758

CXCL17 is a chemokine principally expressed by mucosal tissues, where it facilitates chemotaxis of monocytes, dendritic cells, and macrophages and has antimicrobial properties. CXCL17 is also implicated in the pathology of inflammatory disorders and... Read More about CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans.

Role of endothelin ETA receptors in the hypertension induced by the VEGFR-2 kinase inhibitors axitinib and lenvatinib in conscious freely-moving rats (2023)
Journal Article
Pannucci, P., Van Daele, M., Cooper, S. L., Wragg, E. S., March, J., Groenen, M., …Woolard, J. (2023). Role of endothelin ETA receptors in the hypertension induced by the VEGFR-2 kinase inhibitors axitinib and lenvatinib in conscious freely-moving rats. Biochemical Pharmacology, Article 116007. https://doi.org/10.1016/j.bcp.2023.116007

Receptor tyrosine kinase inhibitors (RTKIs) suppress tumour growth by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) which is an important mediator of angiogenesis. Here, we demonstrate that two potent RTKIs, axitinib and lenvatini... Read More about Role of endothelin ETA receptors in the hypertension induced by the VEGFR-2 kinase inhibitors axitinib and lenvatinib in conscious freely-moving rats.

Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3) (2023)
Journal Article
Dekkers, S., Comez, D., Karsai, N., Arimont-Segura, M., Canals, M., Caspar, B., …Stocks, M. J. (2023). Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3). ACS Medicinal Chemistry Letters, 15(1), 143–148. https://doi.org/10.1021/acsmedchemlett.3c00469

The atypical chemokine receptor 3 (ACKR3) is a receptor that induces cancer progression and metastasis in multiple cell types. Therefore, new chemical tools are required to study the role of ACKR3 in cancer and other diseases. In this study, fluoresc... Read More about Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3).

Kinetic analysis of fluorescent ligand binding to cell surface receptors: Insights into conformational changes and allosterism in living cells (2023)
Journal Article
Hill, S. J., & Kilpatrick, L. E. (2023). Kinetic analysis of fluorescent ligand binding to cell surface receptors: Insights into conformational changes and allosterism in living cells. British Journal of Pharmacology, https://doi.org/10.1111/bph.16185

Equilibrium binding assays are one of the mainstays of current drug discovery efforts to evaluate the interaction of drugs with receptors in membranes and intact cells. However, in recent years, there has been increased focus on the kinetics of the d... Read More about Kinetic analysis of fluorescent ligand binding to cell surface receptors: Insights into conformational changes and allosterism in living cells.

Characterisation of tyrosine kinase inhibitor-receptor interactions at VEGFR2 using sunitinib-red and nanoBRET (2023)
Journal Article
Van Daele, M., Kilpatrick, L. E., Woolard, J., & Hill, S. J. (2023). Characterisation of tyrosine kinase inhibitor-receptor interactions at VEGFR2 using sunitinib-red and nanoBRET. Biochemical Pharmacology, 214, Article 115672. https://doi.org/10.1016/j.bcp.2023.115672

Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis, proliferation and migration of vascular endothelial cells. It is well known that cardiovascular safety liability for a wide range of small molecule tyrosine kinase in... Read More about Characterisation of tyrosine kinase inhibitor-receptor interactions at VEGFR2 using sunitinib-red and nanoBRET.

Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells (2023)
Journal Article
Ogrodzinski, L., Platt, S., Goulding, J., Alexander, C., Farr, T. D., Woolard, J., …Kilpatrick, L. E. (2023). Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells. iScience, 26(7), Article 107232. https://doi.org/10.1016/j.isci.2023.107232

E-selectin is expressed on endothelial cells in response to inflammatory cytokines and mediates leukocyte rolling and extravasation. However, studies have been hampered by lack of experimental approaches to monitor expression in real time in living c... Read More about Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells.

Characterisation of IL-23 receptor antagonists and disease relevant mutants using fluorescent probes (2023)
Journal Article
Lay, C. S., Isidro-Llobet, A., Kilpatrick, L. E., Craggs, P. D., & Hill, S. J. (2023). Characterisation of IL-23 receptor antagonists and disease relevant mutants using fluorescent probes. Nature Communications, 14, Article 2882. https://doi.org/10.1038/s41467-023-38541-2

Association of single nucleotide polymorphisms in the IL-23 receptor with several auto-inflammatory diseases, led to the heterodimeric receptor and its cytokine-ligand IL-23, becoming important drug targets. Successful antibody-based therapies direct... Read More about Characterisation of IL-23 receptor antagonists and disease relevant mutants using fluorescent probes.

Plasma membrane preassociation drives β-arrestin coupling to receptors and activation (2023)
Journal Article
Grimes, J., Koszegi, Z., Lanoiselée, Y., Miljus, T., O’Brien, S. L., Stepniewski, T. M., …Calebiro, D. (2023). Plasma membrane preassociation drives β-arrestin coupling to receptors and activation. Cell, 186(10), 2238-2255. https://doi.org/10.1016/j.cell.2023.04.018

β-arrestin plays a key role in G protein-coupled receptor (GPCR) signaling and desensitization. Despite recent structural advances, the mechanisms that govern receptor-β-arrestin interactions at the plasma membrane of living cells remain elusive. Her... Read More about Plasma membrane preassociation drives β-arrestin coupling to receptors and activation.

Small-Molecule Fluorescent Ligands for the CXCR4 Chemokine Receptor (2023)
Journal Article
Dekkers, S., Caspar, B., Goulding, J., Kindon, N. D., Kilpatrick, L. E., Stoddart, L. A., …Stocks, M. J. (2023). Small-Molecule Fluorescent Ligands for the CXCR4 Chemokine Receptor. Journal of Medicinal Chemistry, 66(7), 5208-5222. https://doi.org/10.1021/acs.jmedchem.3c00151

The C-X-C chemokine receptor type 4, or CXCR4, is a chemokine receptor found to promote cancer progression and metastasis of various cancer cell types. To investigate the pharmacology of this receptor, and to further elucidate its role in cancer, nov... Read More about Small-Molecule Fluorescent Ligands for the CXCR4 Chemokine Receptor.

NanoB2 to monitor interactions of ligands with membrane proteins by combining nanobodies and NanoBRET (2023)
Journal Article
van den Bor, J., Bergkamp, N. D., Anbuhl, S. M., Dekker, F., Comez, D., Perez Almeria, C. V., …Heukers, R. (2023). NanoB2 to monitor interactions of ligands with membrane proteins by combining nanobodies and NanoBRET. Cell Reports Methods, 3(3), Article 100422. https://doi.org/10.1016/j.crmeth.2023.100422

The therapeutic potential of ligands targeting disease-associated membrane proteins is predicted by ligand-receptor binding constants, which can be determined using NanoLuciferase (NanoLuc)-based bioluminescence resonance energy transfer (NanoBRET) m... Read More about NanoB2 to monitor interactions of ligands with membrane proteins by combining nanobodies and NanoBRET.

COVID-19-Induced Myocarditis: Pathophysiological Roles of ACE2 and Toll-like Receptors (2023)
Journal Article
Pannucci, P., Jefferson, S. R., Hampshire, J., Cooper, S. L., Hill, S. J., & Woolard, J. (2023). COVID-19-Induced Myocarditis: Pathophysiological Roles of ACE2 and Toll-like Receptors. International Journal of Molecular Sciences, 24(6), Article 5374. https://doi.org/10.3390/ijms24065374

The clinical manifestations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection responsible for coronavirus disease 2019 (COVID-19) commonly include dyspnoea and fatigue, and they primarily involve the lungs. However, extra-... Read More about COVID-19-Induced Myocarditis: Pathophysiological Roles of ACE2 and Toll-like Receptors.

Use of NanoBiT and NanoBRET to characterise interleukin-23 receptor dimer formation in living cells (2022)
Journal Article
Lay, C. S., Kilpatrick, L. E., Craggs, P. D., & Hill, S. J. (2023). Use of NanoBiT and NanoBRET to characterise interleukin-23 receptor dimer formation in living cells. British Journal of Pharmacology, 180(11), 1444-1459. https://doi.org/10.1111/bph.16018

Background and Purpose: Interleukin-23 (IL-23) and its receptor are important drug targets for the treatment of auto-inflammatory diseases. IL-23 binds to a receptor complex composed of two single transmembrane spanning proteins IL23R and IL12Rβ1. In... Read More about Use of NanoBiT and NanoBRET to characterise interleukin-23 receptor dimer formation in living cells.

Kinetic analysis of endogenous β2-adrenoceptor-mediated cAMP GloSensorTM responses in HEK293 cells (2022)
Journal Article
Cullum, S. A., Veprintsev, D. B., & Hill, S. J. (2023). Kinetic analysis of endogenous β2-adrenoceptor-mediated cAMP GloSensorTM responses in HEK293 cells. British Journal of Pharmacology, 180(10), 1304-1315. https://doi.org/10.1111/bph.16008

Background and Aim: Standard pharmacological analysis of agonist activity utilises measurements of receptor-mediated responses at a set time-point, or at the peak response level, to characterise ligands. However, the occurrence of non-equilibrium con... Read More about Kinetic analysis of endogenous β2-adrenoceptor-mediated cAMP GloSensorTM responses in HEK293 cells.

Fluorescently tagged nanobodies and NanoBRET to study ligand-binding and agonist-induced conformational changes of full-length EGFR expressed in living cells (2022)
Journal Article
Comez, D., Glenn, J., Anbuhl, S. M., Heukers, R., Smit, M. J., Hill, S. J., & Kilpatrick, L. E. (2022). Fluorescently tagged nanobodies and NanoBRET to study ligand-binding and agonist-induced conformational changes of full-length EGFR expressed in living cells. Frontiers in Immunology, 13, Article 1006718. https://doi.org/10.3389/fimmu.2022.1006718

Introduction: The Epidermal Growth Factor Receptor is a member of the Erb receptor tyrosine kinase family. It binds several ligands including EGF, betacellulin (BTC) and TGF-α, controls cellular proliferation and invasion and is overexpressed in vari... Read More about Fluorescently tagged nanobodies and NanoBRET to study ligand-binding and agonist-induced conformational changes of full-length EGFR expressed in living cells.

Optimization of Peptide Linker-Based Fluorescent Ligands for the Histamine H1 Receptor (2022)
Journal Article
Kok, Z. Y., Stoddart, L. A., Mistry, S. J., Mocking, T. A., Vischer, H. F., Leurs, R., …Kellam, B. (2022). Optimization of Peptide Linker-Based Fluorescent Ligands for the Histamine H1 Receptor. Journal of Medicinal Chemistry, 65(12), 8258–8288. https://doi.org/10.1021/acs.jmedchem.2c00125

The histamine H1 receptor (H1R) has recently been implicated in mediating cell proliferation and cancer progression, therefore high affinity H1R-selective fluorescent ligands are desirable tools for further investigation of this behaviour in vitro an... Read More about Optimization of Peptide Linker-Based Fluorescent Ligands for the Histamine H1 Receptor.

Involvement of β-adrenoceptors in the cardiovascular responses induced by selective adenosine A2A and A2B receptor agonists (2022)
Journal Article
Wragg, E. S., Pannucci, P., Hill, S. J., Woolard, J., & Cooper, S. L. (2022). Involvement of β-adrenoceptors in the cardiovascular responses induced by selective adenosine A2A and A2B receptor agonists. Pharmacology Research and Perspectives, 10(3), Article e00975. https://doi.org/10.1002/prp2.975

A2A and A2B adenosine receptors produce regionally selective regulation of vascular tone and elicit differing effects on mean arterial pressure (MAP), whilst inducing tachycardia. The tachycardia induced by the stimulation of A2A or A2B receptors has... Read More about Involvement of β-adrenoceptors in the cardiovascular responses induced by selective adenosine A2A and A2B receptor agonists.

Regionally selective cardiovascular responses to adenosine A2A and A2B receptor activation (2022)
Journal Article
Cooper, S. L., Wragg, E. S., Pannucci, P., Soave, M., Hill, S. J., & Woolard, J. (2022). Regionally selective cardiovascular responses to adenosine A2A and A2B receptor activation. FASEB Journal, 36(4), Article e22214. https://doi.org/10.1096/fj.202101945R

Adenosine is a local mediator that regulates changes in the cardiovascular system via activation of four G protein-coupled receptors (A1, A2A, A2B, A3). Here, we have investigated the effect of A2A and A2B-selective agonists on vasodilatation in thre... Read More about Regionally selective cardiovascular responses to adenosine A2A and A2B receptor activation.

Community guidelines for GPCR ligand bias: IUPHAR review 32 (2022)
Journal Article
Kolb, P., Kenakin, T., Alexander, S. P. H., Bermudez, M., Bohn, L. M., Breinholt, C. S., …Gloriam, D. E. (2022). Community guidelines for GPCR ligand bias: IUPHAR review 32. British Journal of Pharmacology, 179(14), 3651-3674. https://doi.org/10.1111/bph.15811

GPCRs modulate a plethora of physiological processes and mediate the effects of one-third of FDA-approved drugs. Depending on which ligand activates a receptor, it can engage different intracellular transducers. This ‘biased signalling’ paradigm requ... Read More about Community guidelines for GPCR ligand bias: IUPHAR review 32.

Role of the renin–angiotensin–aldosterone and kinin–kallikrein systems in the cardiovascular complications of COVID-19 and long COVID (2021)
Journal Article
Cooper, S. L., Boyle, E., Jefferson, S. R., Heslop, C. R. A., Mohan, P., Mohanraj, G. G. J., …Woolard, J. (2021). Role of the renin–angiotensin–aldosterone and kinin–kallikrein systems in the cardiovascular complications of COVID-19 and long COVID. International Journal of Molecular Sciences, 22(15), Article 8255. https://doi.org/10.3390/ijms22158255

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although COVID-19 has a respiratory foc... Read More about Role of the renin–angiotensin–aldosterone and kinin–kallikrein systems in the cardiovascular complications of COVID-19 and long COVID.

Probing the binding of interleukin-23 to individual receptor components and the IL-23 heteromeric receptor complex in living cells using NanoBRET (2021)
Journal Article
Lay, C. S., Bridges, A., Goulding, J., Briddon, S. J., Soloviev, Z., Craggs, P. D., & Hill, S. J. (2022). Probing the binding of interleukin-23 to individual receptor components and the IL-23 heteromeric receptor complex in living cells using NanoBRET. Cell Chemical Biology, 29(1), 19-29.e6. https://doi.org/10.1016/j.chembiol.2021.05.002

Interleukin-23 (IL-23) is a pro-inflammatory cytokine involved in the host defence against pathogens, but also implicated in the development of several autoimmune disorders. The IL- 23 receptor has become a key target for drug discovery but the exact... Read More about Probing the binding of interleukin-23 to individual receptor components and the IL-23 heteromeric receptor complex in living cells using NanoBRET.